The project will use the Cystic Fibrosis (CF) Foundation Patient Registry (CFFPR) to explore potentially causal relationships between CF causing genetic mutations, airway infections, clinical disease and survival. The CFFPR contains data from over 2 million encounters involving 45,000 patients seen at certified CF care centers in the United States from 1986 through 2011. Our efforts will focus on three specific aims: (1) Develop an explanatory model of survival in CF based on clinically relevant factors; (2) Assess associations between CF mutations, survival and intermediate disease outcomes; (3) Model feedback among mutations, airway infection, clinical disease and survival. Better understanding of the potential pathways that lead from genetic mutation to decreased survival may help clinicians craft individualized treatment plans. Some patients with special vulnerabilities to specific disease complications or infections may benefit from emphasizing specific treatments. For investigators exploring novel medications, our models may identify particular groups of patients to recruit or at least to balance between control and experimental groups. Finally, better pathophysiologic understanding may encourage new directions for exploration in CF, and our methods may be of interest to investigators of other genetic diseases where substantial clinical data sets exist.